Neuronal necrosis in a dog following exposure to an NMDA receptor antagonist

Abstract

N-methyl-D-aspartate (NMDA) receptors constitute one of the three major classes of ionotropic glutamate receptors. We found neuronal necrosis in the brain of one out of four beagles exposed to an NMDA receptor antagonist. The lesions were characterized by shrunken cell bodies with intense cytoplasmic eosinophilia and pyknotic nuclei, and the affected cells were specifically positive for Fluoro-Jade B staining, which has great affinity for degenerating neurons. Bilaterally symmetrical lesions were observed primarily in the dentate gyrus, hippocampus, subiculum and entorhinal cortex. The present case suggests that NMDA receptor antagonism, possibly by altering synaptic transmission via receptors to glutamate within the affected regions, might lead to neuronal necrosis in the canine brain. Other possible pathogeneses include the encephalic ischemic condition associated with seizure activity.